Activation of D1 dopamine receptors stimulates the release of GABA in the basal ganglia of the rat.
ABSTRACT Here we have explored whether dopamine is able to modulate the release of gamma-aminobutyric acid (GABA) from striatal terminals to substantia nigra pars reticulata, entopeduncular nucleus, globus pallidus and caudate-putamen. The type of dopamine receptors involved was assessed by the blocking effect of either SCH 23390 (D1 antagonist) or (-)-sulpiride (D2 antagonist) of the dopamine effect. Dopamine stimulated (EC50 3.2 microM) the depolarization-induced release of [3H]GABA from slices isolated from all of the above mentioned nuclei. SCH 23390 dose-dependently blocked the dopamine stimulation, but (-)-sulpiride did not show any blocking effect. The results suggest that dopamine via D1 receptors modulates the release of GABA from striatal GABAergic terminals.
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ABSTRACT: Presynaptic receptors provide plasticity to GABAergic synapses in the basal ganglia network, in which GABA neurons outnumber all other neurons. Presynaptic receptors, mostly of the metabotropic type, enhance or reduce the strength of synaptic inhibition and are activated by ligands being released from the GABA terminals themselves (autoreceptors) or by ligands coming from other sources (heteroreceptors), including the target neurons innervated by the GABA terminals. The latter mechanism, termed retrograde signaling, is given particular emphasis as far as it occurs in substantia nigra.Progress in brain research 02/2007; 160:245-59. · 4.19 Impact Factor
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ABSTRACT: GABA(B) receptors decrease the release of GABA from the striatal terminals within the pars reticulata of the substantia nigra by opposing the increase in the release caused by dopamine D₁ receptors. The dopamine D₁ receptors also increase the release of glutamate from subthalamic terminals in the pars reticulata. Because GABA(B) receptors decrease the glutamate release from these terminals, we have explored if the effect of GABA(B) receptors also opposed the effect of the dopamine D₁ receptors. The effect of baclofen, a selective GABA(B)-receptor agonist, was tested on the release of [³H]glutamate caused by highly (40 mM) concentrated K(+) solutions in slices of the pars reticulata. Baclofen decreased (the concentration causing 50% inhibition, IC₅₀, was 8.15 μM) the increase in the release of the [³H]glutamate caused by the dopamine D₁ receptors and it also decreased (IC₅₀ was 0.51 μM) this release in the absence of the activation of the dopamine D₁ receptors. The GABA(B) receptors appear then to inhibit glutamate release in two ways; one dependent on the activation of the dopamine D₁ receptors and the other independent of such activation. The protein kinase A-inhibitor H89 blocked the increase in the release of the [³H]glutamate caused by the dopamine D₁ receptors, though it did not block the dopamine D₁ receptor-independent baclofen inhibition of the release. This finding indicates that this inhibition was not via the protein kinase A signal-transduction pathway. N-ethylmaleimide, an alkylating agent that inactivates pertussis toxin-sensitive Gi proteins, eliminated both the dopamine D₁ receptor-dependent and -independent baclofen inhibition, showing that both were mediated by these proteins. The injection of baclofen into the pars reticulata of unanesthetized rats caused contralateral rotation, suggesting a reduced glutamate release from the subthalamic terminals, thereby stopping the inhibition of the premotor thalamic nuclei, causing locomotion. Our data suggest that GABA(B) receptors restrain the excitatory input from the subthalamic nucleus and stimulate motor behavior.European journal of pharmacology 12/2010; 649(1-3):161-7. · 2.59 Impact Factor
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ABSTRACT: Impulse activities were recorded from neurons of the sensorimotor cortex of cats, trained to perform a conditioned placing reaction, before, during, and after iontophoretic application of the synaptically active drugs dopamine (DA) and GABA. Our experiments demonstrated that in most cases isolated application of DA increased the frequency of the impulse activity and the number of spikes related to the placing reaction. On the other hand, GABA evoked decreases in both indexes characterizing the impulse activity. In the case of co-application of DA with GABA, we observed both increases and decreases in the background firing rate activity and in the number of spikes related to the placing reaction. Our results suggest that interaction between the DA-ergic and GABA-ergic systems is realized at the receptor level and cannot be interpreted in an oversimplified manner.Neurophysiology 01/2002; 34(2):213-215. · 0.38 Impact Factor